title: α-Synuclein in cutaneous autonomic nerves.
abstract: OBJECTIVE
  To develop a cutaneous biomarker for Parkinson disease (PD).
  
  
  METHODS
  Twenty patients with PD and 14 age- and sex-matched control subjects underwent examinations, autonomic testing, and skin biopsies at the distal leg, distal thigh, and proximal thigh. α-Synuclein deposition and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. α-Synuclein deposition was normalized to nerve fiber density (the α-synuclein ratio). Results were compared with examination scores and autonomic function testing.
  
  
  RESULTS
  Patients with PD had a distal sensory and autonomic neuropathy characterized by loss of intraepidermal and pilomotor fibers (p < 0.05 vs controls, all sites) and morphologic changes to sudomotor nerve fibers. Patients with PD had greater α-synuclein deposition and higher α-synuclein ratios compared with controls within pilomotor nerves and sudomotor nerves (p < 0.01, all sites) but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores (r = 0.58-0.71, p < 0.01), with sympathetic adrenergic function (r = -0.40 to -0.66, p < 0.01), and with parasympathetic function (r = -0.66 to -0.77, p > 0.01).
  
  
  CONCLUSIONS
  We conclude that α-synuclein deposition is increased in cutaneous sympathetic adrenergic and sympathetic cholinergic fibers but not sensory fibers of patients with PD. Higher α-synuclein deposition is associated with greater autonomic dysfunction and more advanced PD. These data suggest that measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with PD.
authors.affiliation: From the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Ningshan
authors.initials: N
authors.lastname: Wang
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Gibbons
authors.forename: Jacob
authors.initials: J
authors.lastname: Lafo
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
mesh_terms: D000368:Aged; D017776:Autonomic Pathways / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology; D009422:Nervous System Diseases / Q000209:etiology*; D009460:Neurologic Examination; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology; D011187:Posture / Q000502:physiology; D012119:Respiration; D012867:Skin / Q000294:innervation / Q000473:pathology*; D013223:Statistics as Topic; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein